A recent randomized clinical trial suggests that metformin, one of the world’s most commonly prescribed diabetes drugs, may “blunt”—or lessen—the vascular and fitness benefits that typically result from exercise training. Metformin is an oral medication that is widely prescribed as a first-line treatment for type 2 diabetes, which works to help regulate blood sugar levels.
In this 16-week trial, 72 adults participated while researchers monitored how their blood vessels responded to insulin—a key process that enables vessels to widen and efficiently deliver oxygen, hormones, and nutrients throughout the body after meals.
The research investigated whether metformin interferes with the improvements in blood vessel responsiveness to insulin typically seen after exercise. Participants were randomly assigned to either low-intensity or high-intensity aerobic exercise, combined with either a placebo or 2,000 mg of metformin daily.
Those who exercised while taking a placebo showed clear improvements in vascular insulin sensitivity and aerobic fitness. In contrast, participants who took metformin did not see those same benefits. The drug appeared to blunt the positive effects of exercise on both large and small blood vessels.
Typically, exercise helps lower blood sugar levels and enhance physical function, both of which are crucial for effective diabetes management. The study found that if metformin reduces these benefits, patients may get less protection against the disease.
“If you exercise and take metformin and your blood glucose does not go down, that’s a problem,” said Steven Malin, a professor in the Department of Kinesiology and Health in the School of Arts and Sciences and the lead author of the study. “People taking metformin also didn’t gain fitness. That means their physical function isn’t getting better and that could have long-term health risk.”
The impact isn’t just seen in test results—improved fitness gives people more energy for everyday activities, such as climbing stairs, playing with children, or staying socially active. If those gains are limited, it can hurt the overall quality of life, Malin said.
Malin said that the findings don’t suggest that people should stop taking metformin or exercising.
Researchers remain uncertain about the exact reasons metformin dampens exercise benefits. Malin suggests the effect may stem from the drug’s mechanism of action, though more research is needed. With nearly 35 million Americans living with type 2 diabetes, understanding this interaction is crucial.
“We need to figure out how to best recommend exercise with metformin,” Malin said. “We also need to consider how other medications interact with exercise to develop better guidelines for doctors to help people lower chronic disease risk.”